The pineal and retinal melatonin regulates endogenous circadian rhythms, and has various physiological functions including neuromodulatory and vasoactive actions, antioxidative and neuroprotective properties. We have previously demonstrated that the melatonin 1a-receptor (MT1) is localized in human retinal cells and that the expression of MT1 is increased in Alzheimer ’ s disease (AD) patients. We now present the first immunohistochemical evidence for the cellular distribution of the second melatonin receptor, MT2, in the human retina and in AD patients. In elderly controls, MT2 was localized to ganglion and bipolar cells in the inner nuclear layer, and to the inner segments of the photoreceptor cells. In addition, cellular processes in inner and outer plexiform layers were strongly positive for MT2. In AD patients the overall intensity of MT2-staining was distinctly decreased in all observed cellular localizations. Our results indicate that MT2 in the humans, similar to MT1, may indeed be involved in transmitting melatonin ’ s effects in the retina, and AD pathology may impair MT2 expression. Since our previous results showed an increase in MT1 expression in AD retina, the two melatonin receptor subtypes appear to be differentially affected by the course of the neurodegenerative disorder.